Introduction

Since 1993, ephedra has been the source of
tremendous controversy.[1] The FDA has received more complaints on ephedra and
products containing the synthetic form of ephedra (ephedrine) than
any other dietary supplement available to consumers.[2] According to the Journal of Toxicology,
ephedra-based supplements have resulted in cardiac effects, HTN,
intracerebral hemorrhage, nephrolithiasis, mania, and
death.[3] More mild reactions include dizziness, headache,
gastrointestinal stress, irregular heartbeat, and heart
palpitations.[4] The FDA has documented more than 40 deaths and more
than hundreds of serious injuries, but the accuracy of these
numbers have come under suspicion due to the reporting procedures
used to collect the data.[5]

In January of 1999, the FDA listed ephedra at the
top of its priority list for dietary supplements.[6] This announcement falls on the heals of some
dramatic deaths and strokes that have received extensive press
coverage such as the death of Anne Marie Capati.[7] She died after a physical trainer-nutritionist gave
her a list of herbal supplements to take despite her efforts to
inform him of her high blood pressure condition that required her
to take medication.[8]

In February of 2001, a strong message was sent to
the makers of ephedra products to the tune of $13.3 million dollars
intended to compensate Rosalie and Daniel Talbert for
Rosalie’s ensuing stroke after use of the E’Ola product
that was determined to contain ephedrine without indication of the
ingredient on the packaging.[9] This case does not apply directly to ephedra cases
because the problem with this product was its synthetic ephedrine
content, although, it signifies one of the difficulties with
ephedra. Precisely because the product ingredient label stated
ephedra and not ephedrine, it qualifies as a dietary supplement,
which does not fall under the realm of the FDA’s supervisory
safety obligations.[10] The FDA will be holding a public forum soon to
further discuss the future of ephedra.[11]

What is Ephedra?

Ephedra, also known as ma huang, contains the
ephedrine alkaloid that stimulates the central nervous
system.[12] Ephedrine alkaloids have an adrenaline like effect
on the body—it “excites the nervous system, opens blood
vessels, and stimulates the heart.”[13] The ephedra sinica plant contains ephedrine
alkaloids that are used in the herbal supplements once they have
been cultivated from the dried stems of the plant.[14] Some of the main alkaloids in ephedra are
ephedrine and pseudoephedrine, which can be found in OTC drugs, but
an important distinction is that the alkaloids in OTC drugs are
produced synthetically.[15] Synthetic ephedrine is more potent than the
ephedrine alkaloids found in ephedra.[16] Used mainly as a bronchial decongestant,
ephedrine is found in bronchodialators such as Primatene, while
pseudoephedrine is commonly utilized in decongestants such as
Sudafed.[17] Physiologically, it acts to “expand
breathing passages, constrict blood vessels, and increase arterial
blood pressure.”[18] It is the increase in arterial blood pressure that
causes severe hypertension, stroke, or heart attack.[19]

It has gained notoriety for its use as an herbal
supplement that is commonly found in weight loss products
today.[20] Athletic individuals have also been using the
product to reduce their fat to muscle weight ratio.[21] High school and college students have taken
advantage of it to study for long periods of time or late into the
night.[22] Many truck drivers purchase it at truck stops to
help them stay awake on the road, and some people have even used
ephedrine-based products for their diuretic effect.[23] A more dangerous application of ephedrine is its
use to produce amphetamine/hallucinogenic drugs such as
ecstacy.[24] Knock of street drugs such as herbal ecstacy
promising “euphoric stimulation” have added to the
confusion over the safety of ephedra.[25]

The History of Ephedra

Ephedra has been used in a several different ways
(e.g., respiratory infections, asthma, hay fever, chills, lack of
perspiration, headache, and arthritis) in Traditional Chinese
Medicine for more than 5000 years.[26] Ephedra plants were not used only in China, in
fact, references to the plant date back to 1500B.C. in
India.[27] It is documented that the Romans used ephedra as
well.[28] Usage of ephedra in the United States is not new
either (early American settlers used it for tea--known as Mormon
tea).[29] Once an extensive study on the safety of ephedra
was completed by Chen and Schmidt in 1930, doctors in the U.S.
began to prescribe the synthetic form as a treatment for
arthritis.[30] In the 1940s, doctors began to prescribe it more
aggressively for asthma—asthma dosages of 150 mg per day were
not uncommon.[31] Like many other drugs used in Western medicine,
the synthetic form was derived in a laboratory, which eliminates
the dependency on a broker of the herbs.[32] Even aspirin, now synthetically formulated, was
derived from the bark of willow and poplar trees.[33] A laboratory setting makes it possible for
companies to have ultimate control and benefit from financial
savings.

New Uses of Ephedra

While ephedrine has been widely used since the
1930’s in the U.S., it has only recently been discovered to
enhance thermogenesis, which is the process by which calories are
burnt in order to generate heat.[34] This information led to the use of ephedrine in
diet pills such as Phen-fen and ephedra in the herbal alternatives.
Besides being marketed as a "fat burner, ephedra is also marketed
for its energy enhancing capabilities.[35] With increasing demands on our time, these
supplements could seem like a “healthy” alternative to
caffeine, despite the fact that caffeine is often found in the
product as well. It has also become a popular and less expensive
alternative for kids to get a legal “natural” high, but
due to the deaths this product caused, many states have since
banned products like herbal ecstacy or made any ephedrine-based
products available only with a prescription.[36]

A single product that claims to curb your appetite,
increase your energy level, and cause your metabolism to speed up
sounds like a wonder pill if there ever was one. These companies
can capitalize on the fact that obesity is a growing problem in
America. The sales volume reached $278.9 million for diet pills,
showing an increase of 89.6 percent over the sales volume for
1999.[37] More than 97 million adults qualify as obese or
overweight in the United States.[38] The Centers for Disease Control has documented
that the rate of obesity among people ages two to twenty has about
doubled from what it was ten years ago.[39] This younger portion of the population has been
increasingly using products with ephedrine to address this problem.
The fact that most people equate natural with safe has proven to be
fatal for some young teens that have overdosed on supplements with
ephedrine alkaloids.

Generally, Americans are obsessed with losing
weight and are inclined to take the quick-fix route whenever
possible. This mentality coupled with a more is better attitude is
responsible for the abuse of ephedra based products and subsequent
deaths. Because natural products are equated with safety, many
people believe there are no toxic repercussions for exceeding the
recommended dose of a natural dietary supplement.[40] This misperception leads to the occurrence of
overdoses.[41] A lack of consumer awareness regarding the
dangerous effects of this herb is at the root of this problem.

The dietary supplement industry needs to take
responsibility for their role in this lack of knowledge
transference. The Internet poses the largest hurdle to overcome in
terms of false claims. Many products are even described as 100% FDA
approved with no side effects.[42] Given the circumstances in the case of Capati, it
is reasonable to assume that she would not have knowingly risked
her life by talking the supplements had she known of the dangers
and problems associated with combination of prescription drugs and
supplements she ingested.

Manufacturing Situations of Concern

Beyond the isolated question of the safety of
ephedra, there are other considerations regarding safety, although
these are not specific to the ephedra herb. Manufacturers stand to
make enormous profits from fraudulent ingredients or
claims.[43] There are additional issues not listed below, but
I have chosen the ones that most apply to ephedra. Based on
historical occurrences of these situations with herbs, these
concerns are legitimate, and given the serious nature of the
physical effects ephedra can have, these factors merit
discussion.[44]

3. Fraudulent substitution—as in
“chuifong tokuwan”, pills contained modern drugs in
addition to lead and cadmium along with the herbs without
indication on the label.[47] As mentioned earlier, a more recent and relevant
instance of this concern occurred in the E’Ola and Talbert
case in which ephedra was replaced with ephedrine.

Combining Ephedra with Stimulants

Another recent issue surrounding ephedra concerns
combinations of ephedra with other stimulants like caffeine or kola
nut and the irregularity of dosages of ephedra in products, that is
in part a result of the different methods and environments used by
suppliers.[48] According to the hearing testimony before the
House Government Reform Committee on Ma Huang, Dr. Mowrey stated
that adding stimulants to ephedra products is not done to increase
the stimulant effect, but rather to “disinhibit brown adipose
tissue thermogenesis thereby assuring a relatively small dose of
ephedrine will be effective.”[49]

This concept runs counter to the popular rationales
given for the use of stimulants in addition to ephedra. Some
combinations occur unknowingly, such as in the case of Capati and
her prescription medicine. In other instances, those who consume
caffeine in foods or drinks should also be on alert of the effects
additional stimulants can have. A study performed at the University
of California at San Francisco commented on the addition of
stimulants to ephedra products and warned that there is a
"dangerous potentiation effect."[50]

Alternatively, according to Dr. Mowrey's testimony
before the House Government Reform Committee, caffeine additions to
ephedra within products is not dangerous and is in fact necessary
to produce the desired effect when used to address
obesity.[51] Research demonstrates that a minimum of 20 mg of
ephedrine alkaloids and 200 mg of caffeine three times per day is
required in order to be effective--a level that far exceeds the
recently proposed FDA regulation on the standardization of
ephedrine alkaloid quantities.[52] Although, even Dr. Mowrey acknowledges that many
less scrupulous companies add other substances to the ephedra based
products, and it is those substances that are often the culprits of
the adverse effects.[53] He recommends some form of standardization within
reason that is derived from scientific research.[54] A more aware and informed public is necessary in
preventing tragic misuses of ephedra, but part of the current
problem is the mixed information that exists. It is difficult to
get a clear understanding of the safety of ephedra because news
articles, the FDA, and trade associations barrage the American
public with conflicting messages.

The need for more research on dietary supplements
was recognized in 1992 when the United States Public Health Service
established the Office of Alternative Medicine within the National
Institutes of Health (NIH).[55] In 1995, the Office of Dietary Supplements (ODS)
was created by NIH.[56] In 1998, the National Center for Complementary
& Alternative Medicine (NCCAM) replaced the Office of
Alternative Medicine.[57] It was established, among other purposes, to
evaluate herbal medicine.[58] The United States Pharmacopoeia (USP) has also
stated that it is working on creating a monograph for
ephedra.[59] These are steps in the right direction in the
quest to ascertain the safety of dietary supplements such as
ephedra and to demystify them.

Dosage Standards

The lack of standard dosage amounts of ephedrine
alkaloids is a troubling issue to tackle because of the lack of the
FDA authority to regulate the industry, but a recent proposed
regulation in 1997 attempted to do just that—more than 8 mg
per serving would qualify the supplement as adulterated or labeling
that suggested more than a daily intake of 24 mg or more than 8 mg
within 6 hours would fall under regulation according to the Federal
Food, Drug, and Cosmetic Act (FDCA) section 402(a)(1) and
(f)(1).[60] It also limited consumption to one week on the
label of a product.[61] This proposal would have returned broad authority
to the FDA to regulate this herb because the rule did not attempt
to define "serious" or "adverse."[62]

This proposal was not well received by the public.
Restricting the dosage of the product alarms people and the
industry because the action is perceived as a potentially slippery
slope and because there is an enormous discrepancy regarding the
necessity and effectiveness of such a drastic reduction.[63] About 60 percent of Americans take dietary
supplements and they demand unfettered access to these
products.[64] Part of the reason for this increasing portion of
the population consuming dietary supplements is that they wish to
take an active role in their health. Some have become discouraged
with prescriptions that failed to help them, and therefore want to
try a “healthier,” “safer,” more natural
alternative.[65] Today, dietary supplements (including herbal
therapies) are no longer shelved only at health food stores; they
can be purchased at drug and grocery stores.[66] Drug companies and larger-scale manufacturers even
eventually decided to cash in on the dietary supplement
craze.[67] Due to the frenzy this proposal created by
consumers and the dietary supplement industry (a nearly $4 billion
dollar industry that is growing at around 18 percent per year), and
due to the concerns voiced by Congress, the General Accounting
Office, and a directive from the Office of the Inspector General of
the FDA’s parent agency, the Department of Health and Human
Services, the FDA has backed down on this proposed
regulation.[68] The directive instructed the FDA to perform a
complete overhaul on its adverse reporting system. This requirement
stemmed from a new report titled: “Adverse Event Reporting
for Dietary Supplements: An Inadequate Safety Valve” that
found the current system wholly inadequate.[69] The FDA's Center for Food Safety and Applied
Nutrition (CFSAN) has now redirected its efforts from regulating
ephedra to developing a broader strategy to address the
problems.[70]

The Problem Still Exists, but is it a
“Problem?”

So, how much ephedrine is in that bottle? Even if
consumers become more aware and attempt to read labels to avoid
ingesting excessive amounts of ephedrine alkaloids, they may be
making the effort in vein. A study that measured the ephedra
content of 20 ephedra products resulted in a fairly shocking
outcome—half of the products had an ephedra content that was
20 percent higher than stated on the label and one product
exhibited an enormous range of 1.8-10 times the amount depending on
the lot.[71] The "growing conditions, the plant's age, storage,
handling, and preparation" all play a role in the levels of an herb
within a product.[72] But the significance of this information rests on
the premise that ephedra isn’t safe in these higher levels.
If it is indeed safe at higher levels for those individuals who do
not have pre-existing medical conditions, and safe for those who
refrain from combining stimulants, it is possible that these
variances are harmless. Although, for those consumers who choose to
vigilantly monitor their intake levels of ephedra because they wish
to use the product in conjunction with other medications, this
could be fatal.

Products containing extraordinarily high doses of
ephedra should be avoided (a bodybuilder taking 20 mg of ephedra
and 200 mg of caffeine along with a creatine supplement containing
6,000 mg of ma haung (ephedra) daily suffered a stroke in
Dec. 1999).[73] The creatine supplement is extremely popular with
bodybuilders and it is important that the sports community receive
information on the safety of such high levels of ma huang.

Addressing Quality Control

A partial solution that has been suggested is for
manufacturers to adopt the Good Manufacturing Practice (GMP)
standards required of over-the-counter pharmaceuticals, but this
proposal seems to fall short of reality and is not sufficient to
address the issue at hand.[74] The most fraudulent companies producing ephedra
products are not likely to adopt these practices unless required to
do so, and even then, compliance of less than 100 percent would
still leave the consumer vulnerable to choosing a product that does
not use the same standards. Some companies are currently abiding by
the GMP standard.[75] Of course, the label could advertise the
implementation of Good Manufacturing Practices, but this will not
provide much information to the average consumer.

Impetus for Self-Regulation

One incentive to adopt standards is the growing
litigation over ephedra. When using different search engines with
the search term "ephedra," a link to local legal help for ephedra
adverse events is displayed first. The larger manufacturers and
drug companies with deep pockets that now produce dietary
supplements provide a stronger incentive for lawyers to accept
contingency cases of injured parties. Presently, class actions with
this herb are increasing. Recently, a class action suit was filed
in California against the dietary supplement giant Metabolife and
other smaller companies.[76] The class seeks compensatory damages for
neglecting to warn consumers about the possible effects of
ephedra.[77] Many settlements have already occurred regarding
ephedra, and lawsuits have increased with the growing coverage of
this herb.[78] Fortunately, and possibly as a consequence of the
increase in lawsuits, some companies have begun to work with the
FDA to pull their own products when notified of serious side
effects.[79] Other companies have added recommendations to
their product's label instructing consumers to consult a physician
before using the product.[80] (Although, until physicians get up-to-speed with
the dietary supplements, this may not be enough of an action to
stave off an adverse event.) The abundance and likelihood of
ephedra lawsuits should encourage the industry and individual
companies to self-regulate in a more stringent and cautious
manner.

Lawsuits not only involve failure to warn claims,
but also include claims regarding impurity both for substituted
ingredients and differing amounts of an ingredient than purported
on the label.[81] Suits against trainers, nutritionists, health food
stores, and diet counselors will also encourage that proper
warnings are given.[82] A survey given to chain and independent
pharmacists indicated that most pharmacists who would recommend a
standardized herbal formula over a non-standardized one did not
understand the difference between them and did not have a good
grasp of common uses of medicinal herbs.[83]

This startling information shows that a pharmacist
could make a recommendation that a consumer would trust despite the
fact that the pharmacist has little knowledge about herbal
remedies. People in trusted positions must get up to speed with the
latest information on herbal remedies. Even if the evidence is
inconclusive at the moment, the consumer should be made aware of
the potential for interactions with other herbs or medications and
the fact that more is not better with herbs and can lead to serious
injury. Lastly, doctors would not be immune from suit if they have
failed to ask their patients what herbs or supplements they are
taking before prescribing medicine that could lead to an adverse
interaction.[84] A survey conducted by the Beth Israel Deaconess
Medical Center in Boston found that over 70 percent of patients did
not inform their doctors of the alternative therapies they
used.[85] This study furthers the idea that doctors should
have an affirmative duty to ask their patients what dietary
supplements they take. With that responsibility comes
another--obviously the doctors must have some knowledge of dietary
supplements or at least be willing to look up the information.
Information on dietary supplements is vast and confusing, which
means that current doctors will have to school themselves in this
field or go back to school. Medical schools such as Harvard Medical
School are beginning to address this issue by adding courses on
alternative medicine to their medical school curriculum.[86]

Safety

Manufacturers are quick to point out the fact that
an herb such as ephedra has been used for centuries in Chinese
medicine. This type of advertising only fuels the perception that
natural and herbal equals safe. There is an implied "test of time"
guarantee, but last tallied, there is a minimum of six wrongful
death suits against the manufacturer of Nature’s Nutrition
Formula One.[87] The FDA has received more complaints about ephedra
than any other dietary supplement.[88] In response to the complaints they received,
the FDA released a warning regarding this specific product and also
gave out a hotline number for consumers to call.[89] This announcement was followed up by another one
made on April 10, 1996 to healthcare professionals requesting them
to report adverse events to the FDA via Medwatch or the
hotline.[90]

The question on the mind of everyone, including the
FDA, is: Is ephedra safe for consumption? The jury is still out on
this question. One factor that increases the danger of ephedrine
toxicity is its relatively short half-life of six hours to ten
hours--the levels of toxicity can be cumulative when it is ingested
on a regular basis, and the effect is heightened by other the use
of other stimulants like caffeine.[91] Yet, the FDA has itself approved the use of
ephedrine in OTC drugs in dosages of 25 mg per use and up to 150 mg
per day, and declared that ephedrine is “generally recognized
as safe and effective.”[92] This is quite telling because synthetic ephedrine
is stronger than ephedra. Pseudoephedrine was approved for single
doses of 60 mg and 240 mg per day.[93]

The language contained within the Dietary
Supplement Health and Education Act (DSHEA) also leads one to
believe in the safety of virtually all dietary supplements
(“dietary supplements are safe within a broad range of
intake, and safety problems with the supplements are relatively
rare”).[94] Adversaries of the FDA’s desire to regulate
ephedra would provide statistics about the relative safety of
ephedra versus prescription drugs, and remind the reader that the
causal link of most of the adverse events with ephedra has not been
established. Moreover, millions of doses of ephedra are taken each
year by Americans without serious repercussions.[95] This illustrates that the herb can be safe if used
as directed. This assertion is supported by Dr. Mowrey's review of
the FDA's AER list--he found that none of the serious adverse
events had occurred when the product when the product was ingested
properly.[96]

However, Dr. Mowrey also downplays the significance
or correlation of those who have died and their consumption of
ephedra. For example, he stated, "Hundreds of people die in doctors
offices while on treadmills. Is it a surprise, then, that out of
the millions of Americans using ma haung, one of them happens to
experience exercise-related injuries?"[97] There is logic in this statement, but the issue
should also not be summarily dismissed so quickly. It has become
apparent that certain groups are at risk such as the 17-year-old
high school football player who reportedly never exceeded the
recommended dosage and died of a heart attack caused by ephedrine
toxicity.[98]

Regardless of the problems with the reporting
procedures used in the AEMS, one thing is clear: many of those
complaining of adverse events have misused or abused
ephedra.[99] During a testimony by Theodore M. Farber, PhD, he
explained that most people reporting negative effects “had
hypertension, were diabetic, had a family history of heart disease
or were taking other medications—one person was taking 85
pills a day.”[100] It is certain that people with previous
conditions including but not limited to heart conditions, elevated
blood pressure, asthma (and are on medication), diabetes, or
glaucoma should not take this product.[101] Or, at a minimum, a doctor should be
consulted.[102]

Unfortunately, sensitivities are impossible to
predict for even healthy individuals.[103] According to Anthony Almada, president and
chief science officer of Imaginutrition, a natural products
consulting group, 20 percent of 100 people in a recent study on
ephedra quit because they simply “couldn’t handle
ephedra.”[104] For this reason, consulting a doctor even if you
currently have no known health concerns would be wise. An herb
expert, Varro Tyler, PhD, strongly recommends people be supervised
by a physician if they wish to use ephedra for longer than seven
days.[105] A doctor can aid in the prevention of a serious
health problem by monitoring the vital signs of the
patient.[106] For those who cannot afford this monitoring,
serious consideration should be given to the reasons for taking the
herb and other stimulants should be avoided completely. This herb
is meant to provide initial assistance and not long-term aid for
dieters.[107] Some experts believe that the "long-term use of
stimulants is not advised because they keep the body in a constant
'fight or flight' mode, rapidly depleting its energy reserves and
potentially leading to a variety of disorders."[108] More mild side effects like insomnia or
headaches can also occur, which should provide alternative
incentives to avoid prolonged usage.[109]

Other healthcare professionals would argue
vehemently against the assertion that the product cannot or should
not be used for a long-term diet aid. A six-month clinical trial
study conducted at Columbia University found that ephedra did aid
participants in losing weight and increased their energy
level.[110] The patients receiving ephedra lost twice the
amount of weight the patients receiving a placebo lost.[111] Nevertheless, long- range studies need to be
performed. Regardless of which camp you decide to join, it does
seem evident that until more extensive research is done, and until
more thorough data can be compiled on the adverse effects of the
herb, a physician should be consulted for long-term use to ensure
that the regimen is appropriate.

In fact, the Council for Responsible Nutrition
sought to provide clarity on the topic by hiring a scientific
consulting firm, Cantox Health Sciences, to determine the safe
dosage and overall safety of ephedra from 19 ephedra
studies.[112] According to council President, John Cordaro,
"The totality of information showed a consistency that was
compelling." They concluded that 90 mg doses per day were in fact
safe for most people.[113] Those thought to be at risk and therefore should
not take the ephedra are: anyone under 18, people with heart
disease, diabetes, glaucoma, high blood pressure, thyroid disease,
kidney impairment, or enlarged prostates, or pregnant or nursing
women.[114] The report recommends that the label reflect
these at risk groups in the form of a warning.[115]

The results of this report were similar to another
industry-sponsored study performed by Harvard and
Columbia.[116] After glancing at the list of those in the at
risk group, it is difficult to not worry about the marketing and
use of ephedra for weight loss in obese individuals. Many severely
overweight individuals would be the ones who would fall into the at
risk category because they often have high blood pressure or
diabetes, which heightens the necessity to have these warnings
placed on product labels. These reports help to illuminate the
safety question, and address the likelihood of adverse events in
certain groups. Additional studies are vital considering that the
adverse effects are thought to be at least tenfold the number the
FDA has recorded.[117]

German Commission E Monographs

The German Commission E was founded in
1978.[118] On January 17, 1991, they published a monograph
on ephedra.[119] One reason for the creation of this commission
is that herbal medicines account for 30 percent of the drugs sold
in pharmacies there.[120] Herbs require the E marking to be on the
market.[121] A critical difference is that over half of the
herbs are actually prescribed by physicians.[122] A 1997 poll on the use of herbal medicines
showed that two-thirds of those polled took herbal medicines and of
these two-thirds, 72 percent had a minimum of some college
education.[123] The phytopharmaceutical companies sponsored the
testing of ephedra's toxicity, which is possibly the reason that
the toxic effects are less comprehensive in this report than in
The Laurence Review of Natural Products.[124]

The German Commission E lists the uses,
contraindications, side effects, interactions with other drugs,
recommended dosages, mode and duration of administration for
ephedra.[125] Interestingly, weight management and increased
energy are not included in uses.[126] Furthermore, the potential for fatal effects
is absent.[127] Strangely, under higher dosages, development of
dependency is listed.[128] Interactions with other drugs include: "cardiac
glycosides or halothane, which results in the disturbance of the
heart rhythm; guanethidine and MAO-inhibitors, which lead to an
enhancement of the sympathomimetic action of ephedrine; and
finally, decale alkaloid derivatives or oxytocin, which can cause
the development of hypertension."[129] Adult dosage is set at 15-30 mg per dose with
a daily maximum of 300 mg.[130] Children are limited to .5 mg of total ephedrine
alkaloid per kg of body weight with a daily maximum of 2 mg of
total ephedrine alkaloid per kg of body weight.[131] The duration of administration states that this
herb is for short-term use only "because of tachyphylaxis and
danger of addiction."[132]

In a note, the International Olympic Committee and
the German Sports Association have qualified ephedra as
addictive.[133] However, Edgar H. Adams, M.S., Sc.D., former
Director of the Division of Epidemiology and Statistical Analysis
at the U.S. National Institute on Drug Abuse, provides a more
current evaluation of ephedra.[134] He found no reason to believe that this herb
possesses addictive qualities.[135] Although, he did not categorically rule out the
possibility, he did state that the likelihood was low and not
certain enough to merit regulatory control.[136]

It was the American Botanical Council (ABC) that
made the highly anticipated English translation available.[137] Well-respected professionals such as Professor
Varro Tyler and Dr. Andrew Weil touted this publication as offering
the most accurate information in the world--a reference guide that
doctors can trust.[138] But, the monographs in this guide are incredibly
brief with very little detail.[139] In fact, references to literature are
conspicuously absent, which diminishes their value as a complete
resource because the rationale for the decisions made is not
ascertainable.[140] Regarding this flaw, Professor Heinz Schilcher,
the Vice President of the Commission, divulged that speculation
rather than scientific data is sometimes used to reach some
conclusions that appear in the monographs.[141] This is disconcerting when the monographs have
received such acclaim and praise for being the most scientific and
trustworthy source of information on herbs.[142] Some physicians and pharmacists have begun to
cite Commission E monographs as immutable truths, which is cause
for alarm when it is known that the monographs do contain some
mistakes, omissions, and speculations.[143]

The recommended dosages may also present a problem
when applied in the United States.[144] For example, the ephedra dosages are listed
for the preparation of the dried herb for German aqueous infusions
or decoctions, but in the United States the hydroethanolic extracts
are usually taken from fresh and not dried herbs, and the
conversion needed can be complex.[145] Similarly, the use of standardized herbal
material, occurring more frequently, makes the task of correlating
the standardized herbal material to the infusion based dose data in
the monographs more difficult.[146] Another topic of concern relating to the
monographs and the ephedra monograph specifically, is the lack of
available studies at the time.[147] This could drastically impact the
recommendations the Commission made.[148]

In spite of the flaws contained in the German
Commission E Monographs, the American Botanical Council believes
that the "Commission E system can provide an excellent model for
regulatory reform, in the United States and possibly other
countries, by providing a rational process for reviewing herbs and
phytomedicines for their safety and efficacy."[149] Naturally, ABC has an incentive in pushing the
authoritative nature of this work.[150] It can add to the credibility of the use of
herbs for medicinal purposes, which aids in solidifying their role
as intermediary between the industry, physicians, and the
FDA.[151] It is valuable to avoid over-inflating the worth
of this publication because it should not be the only source
consulted, nor should the herbal industry be lulled into thinking
that further substantial efforts in creating more useful and
detailed monographs is not a priority. Nevertheless, the German
Commission E monographs are a starting point that we can learn from
and improve upon.

The History of Dietary Supplement
Regulation

Some senators remarked that the lobbying efforts
for the Dietary Supplement Health and Education Act (DSHEA)
paralleled the Vietnam War.[152] “Many members of the House of
Representatives and Senate stated that they were receiving more
mail, more phone calls, and generally more constituent pressure on
this subject than on anything else—including health care
reform, abortion, or the deficit.”[153] At that time, there was a commonly held belief
that the FDA was regulating the dietary supplement with an iron
fist. Consumers wanted access to herbs and supplements without
being forced to wait for FDA approval. The combination of the mass
campaign and the underlying argument that health of Americans
should be a priority and that the “importance of nutrition
and the benefits of dietary supplements to health promotion and
disease prevention have been documented increasingly in scientific
studies.”[154]

As a result, DSHEA was passed and was signed into
law by the President on October 25, 1994, but took effect in 1996.
This was a watershed event for the dietary supplement industry and
consumers of their products. The amendment was enacted to appease
the American public and the dietary industry and to ensure the
availability of products that are accurately labeled and
safe.[155] The language of the statute even indicated that
the FDA had taken on too much of a big brother role in regulating
dietary supplements. This is evidenced in the warning sentence:
“the Federal Government should not take any actions to impose
unreasonable regulatory barriers limiting or slowing the flow of
safe products and accurate information to consumers.”
President Clinton’s statement to the public upon signing the
legislation reflected this sentiment.[156] He declared that the FDA had complicated the
decisions consumers needed to make and “paradoxically limited
the information to make healthful choices.”[157]

This Act basically amended the portion of the
Federal Food, Drug, and Cosmetic Act (FDCA) dealing with dietary
supplements and their dietary ingredients.[158] Herbs fell under the rubric of dietary
supplements because DSHEA defined a dietary supplement as product
meant to supplement the diet that contained "herbs or other
botanical substances, amino acids, vitamins or minerals, or a
combination of these."[159] Prior to DSHEA, dietary supplement companies
were required to pass the “new drug approval” (NDA)
process, which included submitting pre-market evaluations on the
safety and efficacy of the new product, and the FDA was able to
determine whether the labels were misleading or easily
understandable.[160] Most herbs never made it through the NDA
process, which was partially due to the fact that companies had no
incentive to spend substantial amounts of capital on the research
for the required safety and efficacy substantiation because herbs
cannot be patented.[161] Under DSHEA, this pre-market approval
information was no longer necessary and the barrier to market entry
was removed.[162] A safe harbor was created for companies to
manufacture herbal remedies that would be classified as dietary
supplements.[163] This classification blocks the FDA from
regulating the herbal products as food additives, which would have
given them more regulatory authority.[164]

DSHEA dramatically affected labeling of dietary
supplement products. It requires that products be clearly labeled
as dietary supplements, and have the name and quantity of each
ingredient on the label.[165] If it is a combination product, the label must
list the total amount of non-inert ingredients.[166] An herbal product must state the specific part
of the plant from which it was derived.[167] Nutrition information in order of most
significant amounts for which the FDA has established guidelines is
also required. Section six of DSHEA has had the greatest impact on
the dietary supplement industry's ability to market their products.
It enabled manufacturers of herbal products to make
structure-function claims on the packing of their
products.[168] Section six defines when a statement is
acceptable: “The statement claims a benefit related to a
classical nutrient deficiency disease and discloses the prevalence
of such disease in the United States, describes the role of a
nutrient or dietary ingredient intended to affect the structure or
function in humans, characterizes the documented mechanism by which
a nutrient or dietary ingredient acts to maintain such structure or
function, or describes general well-being from consumption of a
nutrient or dietary ingredients.”[169]

For example, a company producing Valerian cannot
state that the product cures insomnia, but it can refer to the
products’ ability to “promote restful sleep”
provided that it also includes a disclaimer that “this
statement has not been evaluated by the Food and Drug
Administration. This product is not meant to diagnose, treat, cure,
or prevent any disease.”[170] This tacked on statement does not sufficiently
indicate that the consumer should be cautious. As evidenced by the
example above, the structure/function claims can be misleading and
certainly the average or even above average consumer is not
knowledgeable about the blurred demarcation and will not think
critically about the fact that the claim does not affirmatively
proclaim to cure insomnia. Consequently, the structure/function
claim standard, third-party marketing materials, and statements
such as "this product has recognized healing properties" has fueled
the natural equals safe perception and enhanced consumers
unquestioning belief in the efficacy of the products.[171]

In February of 1996, the appointed Commission on
Dietary Supplement Labels (a commission provided for in DSHEA) had
their first meeting.[172] In a 1997 report, they suggested that dietary
supplement manufacturers should bear the burden of self-regulation
in regards to the warning labels and safety of their
products.[173] The commission has advised against misleading
consumers with product labels, and has suggested that unverified
claims should be blatantly qualified.[174] They also strongly advised the industry to
provide unbiased material on the products that addresses evidence
of nutritional support, product safety for its intended use, and
safety of dosages.[175] While these are all useful suggestions, it is
the implementation and incentive for implementation that has been
lacking.

DSHEA also affected the FDA’s ability to
establish a case that a product was in fact a new drug by banning
the use of advertisement claims of products in publications
associated with the sale of supplements in order to aid in
demonstrating improper labeling.[176] These publications could not be attached to
the product directly, push a specific brand or manufacturer, be
false or misleading, and the publication needed to offer a balanced
presentation of the available scientific information.[177] And, once again, the FDA bears the burden of
substantiating any infraction of this provision.[178] The consequence of this section of DSHEA is an
ability on the part of manufacturers of dietary supplements to make
claims and representations that could not otherwise be made. These
publications have aided in the perception that dietary supplements
are safe and certain herbs or supplements can be a panacea.

DSHEA does provide two methods of regulation as
long as a dietary supplement or an ingredient qualifies as
adulterated.[179] In order to fall under this provision, the
supplement or ingredient must “present a significant or
unreasonable risk of illness or injury under conditions of use
recommended or suggested in the labeling, or if no condition of use
are suggested or recommended in the labeling, under ordinary
conditions of use.”[180] Essentially, the supplement or ingredient must
place the public in a position of significant risk for imminent
harm.[181] The United States bears the burden of proof of
establishing the above conditions.[182] More importantly, if the FDA were to attempt
to enforce a new regulation regarding a dietary supplement, the FDA
would still be forced to demonstrate the dietary supplement was
adulterated.[183] Basically, dietary supplements are regulated as
foods.[184] Companies manufacturing herbal products do not
have to conform to a standard dosage or strength.[185] As a result, the FDA has been placed in position
of "regulating by news release."[186]

The Flaws of the FDA’s Collection of
Adverse Event Reports

Because the FDA cannot regulate dietary supplements
as drugs, it is relegated to a watch and wait position. It needs to
provide conclusive evidence that a product is unsafe for
consumption before it can ban or remove a dietary supplement from
the market.[187] It is for this reason that the effectiveness of
collecting information on the safety of dietary supplements is
imperative. The FDA’s Adverse Event Monitoring System (AEMS)
was designed to aid them in assessing hazards connected to specific
dietary supplements and alerting the public of any safety issues
with these products.[188] The AEMS was designed to “1.detect adverse
events, 2.generate signals of possible public health concerns,
3.assess those signals, and 4.take appropriate safety actions based
on its assessment.”[189] One large fault of the reporting system is that
the adverse event may or may not be associated with the injury
because confirmation is not guaranteed.[190] Moreover, the reporting of an event is not
compulsory, so it is unclear how many other adverse events are
occurring from ephedra.[191] One company has admitted to receiving 3,500
consumer complaints that were never reported to the FDA.[192] Based on the FDA’s conclusion of the risk
posed to the public (experts and/or studies are used to determine
this), the FDA will issue warnings, alerts, request a product
recall, or seize a product.[193] Because the results of AEMS for ephedra led the
FDA to propose a new regulation to limit the amount of ephedrine
alkaloids within a product, the flaws of the AEMS are crucial to
this validity or necessity of this proposal. Due to strong
criticism, the FDA has since withdrawn this controversial
proposal.[194]

A recent study commissioned by the FDA found that
the FDA receives reports on under one percent of the actual adverse
events that occur, which is thought to be a result of the
consumers’ belief that natural equals safe, the fact that
these products are used without a doctor’s supervision, and
because consumers are not aware they should contact the
FDA.[195] Many consumers contact the company instead, and
the company certainly has no incentive to report adverse incidents
to the FDA—quite to the contrary, doing so could negatively
impact their financial earnings. Unless the company is aware of a
deadly result or serious deviation in their formula causing serious
bodily injury, they are not likely to contact the FDA (if such a
serious outcome were likely, they would be motivated to make every
possible attempt to correct the problem in order to avoid class
action and individual suits that could leave them bankrupt).

Missing data is another obstacle in the way of
validly interpreting the safety of particular dietary supplements.
The FDA lacks the medical records tied to the events reported,
which is in part due to the fact that only 20 percent of adverse
event reports originate from a doctor.[196] It also has inadequate information on the
products consumers or doctors cite as the cause of their
symptoms.[197] Surprisingly, the FDA is unaware of the
ingredients contained in 32 percent of the reported problematic
products, does not have the labels of 77 percent of the
“problem” products, and had not obtained samples for 69
percent of the reported products.[198] Other substantial flaws include the inability
to ascertain the manufacturer for 32 percent of the products, and
the inability to follow-up with callers flagged for follow-up due
to inadequate contact information.[199]

All the aforementioned defects leave the FDA
incapable of analyzing the data in a meaningful way.[200] This relates directly to their ability to
establish a connection between the reports and the safety of the
products. At this point, the FDA does not have enough clinical
information on the dietary supplements on the market because it is
not required of the manufacturers (there is an exception that
affects a small number of manufactures—certain new dietary
ingredients must submit “relevant” safety information
75 days prior to market introduction), but more clinical
information is becoming available on almost a daily basis.[201] Another essential missing data point is the
total number of consumers who take a specific product.[202]

The lack of comprehensive data necessarily leads to
inaction on the part of the FDA. Any action taken would be attacked
severely, which is evidenced by the proposed regulation to limit
the allowed dosage of ephedra. Instead, the FDA has relied on its
website to inform the public, but this site is inadequate because
it is not updated regularly, and according to the report by the
Office of the Inspector General (OIG), the site “contains
misleading information.”[203] Because consumers need to be informed, changes
must be made to the adverse event monitoring system. The present
system has very little scientific value because of the gaps of
information and lack of follow-up data. Therefore, the OIG has
published a report on the AEMS and made recommendations for the FDA
to follow.

OIG Recommendations for the FDA

OIG determined that the entire framework of the
AEMS requires modification and some legislative or regulatory
alterations will be necessary in addition to more funding to
execute the changes.[204] The FDA has responded positively to the
suggestions by listing many of them as their top priorities for the
year and in their 10-year strategic plan for

dietary supplements.[205] I have included the majority of the
information from the report because of its relevance to the future
of the FDA’s treatment of ephedra. Moreover,

because the report was only released in April, it
has not received extensive written treatment.

Demand that manufacturers of supplements notify the FDA of any
serious adverse effects for certain products.[207] This recommendation will force the FDA to draw a
bright line for products or ingredients that will be subject to
this requirement.

Establish a contract with the Poison Control Centers to have
access to their adverse event reports on dietary
supplements.[208] These reports will provide useful safety
data.

Provide information to professionals in the healthcare industry
and consumers about the AEMS for dietary supplements.[209] One suggestion for implementation of this
recommendation was to require manufacturers to include their own
toll-free number or the toll-free number of the FDA, and to enlarge
the program for informing doctors of current information on dietary
supplements.[210]

Recommendation 2: “Obtain more information on adverse
event reports in order to generate stronger signals of public
health concerns.”[211]

Promote educational programs for increased understanding within
the health professional's community on how essential the inclusion
of medical information in adverse event reports is.[212] This information will enable the FDA to more
effectively draw conclusions about the safety of the
supplement.

Make it mandatory that dietary supplement manufacturers
register their products with the FDA.[213] This would be one of the most useful, yet
difficult recommendations to implement. This would address their
inability to discern the manufacturers of products in
question.

Demand that dietary supplement manufacturers register with the
FDA.[214]

Communicate serious adverse event reports to manufacturers upon
receiving them at the FDA.[215] This would allow the manufacturers to address
the problem as quickly as possible if it was deemed necessary after
further testing.

Relay the significance of self-identification to health
professionals and consumers.[216] This ensures that the FDA can gather any
necessary follow-up information.

Acquire a new computer system that will track and analyze
adverse event reports.[217] This would give the FDA the ability to
slice-and-dice the information within the database based upon the
desired information.

Provide more direction regarding the specific safety
information desired by the manufacturers who currently are required
to submit a 75-day pre-market notification for new dietary
supplement ingredients.[219] This is already within the sphere of FDA
control, and therefore, the FDA shouldn’t waste a low cost
opportunity to gain more information.

Look into the option of a monograph system for dietary
supplements, which is a system that details that details efficacy
and safety information on certain ingredients.[220]

Work with the National Institutes of Health in order to agree
upon and establish an agenda to target safety concerns.[221]

Help the industry and the United State Pharmacopoeia to
implement standardization with supplement ingredients, namely
botanicals.[222]

Facilitate the rapid development and execution of Good
Manufacturing Practices for manufacturers of dietary
supplements.[223] This would necessary for implementation of the
standardization of ingredients.[224]

Recommendation 4: “Disclose more useful information to
the public about dietary supplement adverse events.”[225]

More useful and up-to-date information is needed on the FDA
website.

Summarize reported data in order to discern causation.

Response from the Trade Associations

The trade associations reviewed the report and
offered three main criticisms: 1. the report does not attempt to
address the internal operating procedures of the FDA’s AEMS,
2. the report did not take DSHEA into consideration in the
recommendations section, and 3. it did fail to factor the desire of
the public to have control over/access to their
“self-care” products.[226] All these concerns have merit, yet it is
clear that change needs to occur within the AEMS. It is now a
matter of developing the most practical, cost-effective, and useful
solution.

The Consumer Healthcare Products Association (CHPA)
has led a consortium of dietary supplement trade groups to join
forces in an effort to work together to petition the FDA to enforce
a nationally standardized formulation, labeling, and marketing of
ephedra.[227] They have requested synthetic ingredients and
unlawful claims to be vigilantly monitored and swiftly acted
upon.[228] They have stressed that action against companies
engaging in fraudulent practices be taken because those companies
have a detrimental effect on the compliant companies.[229] CRN would also like to see more publicity
regarding the new, more active enforcement the FDA plans to
initiate in hopes of deterring companies from carrying out
fraudulent plans.[230] The companies currently participating in
self-imposed standardization does not definitively qualify the
product as safe.[231] Additional research is needed to determine safe
and effective levels of ephedra. Until more studies are done,
caution should still be exercised with this product, but
standardization is a move in a positive direction.

Some are pointing the finger at the prescription
and non-prescription pharmaceutical weight loss industry for
wielding their power and influence to sway the FDA to regulate, as
increased regulation will help ensure their profitability. Products
containing ephedra are competing with their brands and affecting
their market share. Recently, the dietary supplement industry
pushed for legislation that would prevent states from banning
ephedra and other herbal products.[232] This bill is titled the National Food
Uniformity Act of 2000.[233]

States Respond by Regulating
Ephedra

At least 17 states (Arizona, Arkansas, California,
Florida, Hawaii, Idaho, Louisiana, Missouri, Nebraska, Nevada, New
Mexico, Ohio, Oklahoma, Oregon, Tennessee, Texas, and Virginia) now
have passed some form of legislation restricting the sale of
ephedrine based products.[234] Some states have been much tougher on ephedra
than others. For example, Ohio has classified products containing
ephedrine as schedule V controlled substances.[235] Schedule V restrictions require that the
supplement be dispensed by a pharmacist in amounts no greater than
100 in any 30 day period.[236] Purchasers must be 18 years of age with valid
identification, and they must give their address and
signature.[237] Florida has made ephedra available by
prescription only, and has limited the claims allowed on
packaging.[238]

To Regulate or Not to Regulate

"Do we want to restrict the freedom of millions
just to protect the health of a few foolish zealots?"[239] Some would answer this question with a
resounding "yes." The FDA has been in a difficult position and is
often accused of doing nothing or attempting to do too much.

Ephedra may be useful in reducing total obesity
related medical costs. Even a 5-10 percent decrease in weight can
"lead to enormous medical benefits, such as improvements in blood
pressure, lipids, and blood glucose, as well as a rise in
self-esteem and a lowering of depression."[240] The immediate key to avoiding the serious
injuries is education. Many overweight consumers are so desperate
to lose weight that they increase their intake of the ephedra. For
example, one woman consumed over 28,000 mg of ephedra per day,
which led to acute paranoid psychosis.[241] Consumers need to know and understand the risks
they are taking with ephedra.

Ephedra is an herb that mimics the effects of drugs
requiring a prescription, but it is regulated as a food. An
attorney who handled an ephedrine case in Florida remarked that if
an herb has the same physiological effect on the body as a
synthetically produced version, it ought to be regulated ("if it
acts like a drug, it should be tested and regulated like a
drug").[242] Perhaps strict regulation is not the answer and
would run counter to the intent of Congress as memorialized in
DSHEA. There may be other alternatives to regulation or another
form of regulation that would not hamper companies from producing
safe and healthy products that consumers want access to.

At least for the moment, the industry and consumers
alike can rest easy because of CFSAN's decision to focus on
creating strategy to address the problems with the adverse event
reports rather than propose regulations. Their goal in regards to
the AEMS is to create a system that makes adverse event reports
"promptly available to manufacturers that includes the timely
redaction of confidential information" and allows for follow-up
investigations and clinical assessments.[243] The president of a Washington, D.C.-based trade
association, Council for Responsible Nutrition, that represents a
large portion of the ingredient suppliers and finished product
manufacturers, stated that the FDA needed to hone their
agenda.[244] The US General Accounting Office offered the
same criticism.[245] In its present form, the plan is not actionable
because it is too broad in scope and doesn't provide a detailed
plan to facilitate change.[246]

As of April 2000, the FDA began to consider a new
proposal to ban any products that combine ephedra and other
stimulants.[247] Given the current conflicting and paltry
research available on the interaction effects of ephedra, it seems
that any proposal limiting the combinations in question would be
premature. At this point, it would appear more sensible to focus on
finding a way to regulate the unsafe products produced by companies
that are inadequately or falsely labeled, or have patently
questionable amounts of ingredients.

Realistically, any drastic regulatory solutions
will be met with such a powerful opposition from the industry and
consumers that the proposals would stand slim chance if any of
becoming final rules, as witnessed with the FDA's recent
short-lived proposal to restrict the use of ephedra. Significant
public outcry will be necessary to amend DSHEA. According to a
recent study completed by National Public Radio, the Kaiser
Foundation, and the Kennedy School of Government, consumers are in
fact now wanting stepped up governmental regulation for dietary
supplements to ensure purity and safety, and to qualify the
veracity of health claims made in advertisements and on
labels.[248] It may just be a matter of time before the
pendulum swings back toward the direction of greater regulation,
especially if that regulatory scheme will allow access to products
without reducing the information consumers seek.

Until the backlash occurs, the FTC can play a more
extensive role in the regulation of dietary supplements. While
DSHEA left the FDA with substantially less authority to regulate
the dietary supplement industry, the FTC has maintained its ability
to challenge the health claims and deceptive advertising of
manufacturers.[249] Manufacturers must demonstrate a "reasonable
basis" for the claims and/or advertising, which translates into
"competent and reliable scientific evidence" from objective studies
conducted by experts.[250] However, the FTC cannot require a company to
test the product to ensure it is safe at the recommended dose, nor
can it force a company to include a warning about harmful side
effects.[251] Nevertheless, the FTC has been somewhat
successful in their regulation attempts (both in court and with
administrative orders), but they could be more vigilant in their
policing efforts, which would aid both the FDA and the American
public.[252]

While stepped up efforts by the FTC will be
helpful, the FTC alone can not rectify the situation. Dr. Mowrey
testified before the House Government Reform Committee that he
believes the answer may lie in a new regulatory category such as
"medicinal foods."[253] Another suggestion was the creation of a
category called traditional herbal therapies.[254] This idea has merit because the FDA would not be
forced to impose a pre-existing and ill-fitting structure upon
dietary supplements. It is possible that a new regulatory category
could work in the future if it took into consideration the
constraints of the dietary supplement industry regarding scientific
proof and did not deny consumers access to products based on
insufficient safety data. A new category should at least tackle the
current problems with misleading labeling and should begin to
address the task of collecting more scientific data on these
dietary supplements in order to better ascertain the safety and
proper dosages and interactions of the supplements. However, even
this proposal would meet strong objections from the industry
stemming from a fear of a reduction of control. For this reason,
the immediate focus should be on affecting change that is possible
within the immediate future.

FDA Action Plan

Despite the FDA's plans for change, trade
associations and the GPO have criticized the lack of definite
deadlines for execution. In defense of the FDA, without the
allocation of funds for this project, it is not possible to
implement all the changes and any deadlines would be knowingly
unattainable. Funding from Congress must be increased if the FDA is
to carry out its responsibilities effectively. Critics of the FDA
such as Senator Orrin Hatch and Representative Bill Richardson,
agree that "greater consumer knowledge about preventative medicine
should be encouraged," yet more funding is a prerequisite for this
to occur.[255]

Guidelines

FDA guidelines are an alternative to regulation
that is realizable without immense cost or long delays. The
guidelines could be updated once comprehensive studies are
performed, but until then, the available assembled data could be
used. The updates to the guidelines could be implemented
efficiently because they do not have the force and effect of law
and accordingly would not have to go through the same channels as
regulations. This allows the FDA to abide by DSHEA and the intent
of Congress, and does not require the substantial additional
funding or delays that many other options would. The guideline
could signify the position of the FDA and be used in court to
establish the FDA's views regarding the issue at hand. The FDA
policy on guidelines allows the FDA to "establish principles or
practices of general applicability that relate to performance
characteristics,...product standards,...compliance criteria,...and
ingredient specifications."[256] According to FDA procedures, the Center director
would possess the authority to change the guidelines.[257]

Good Manufacturing Processes

Another initiative the FDA can take that does not
require funding that can assist in moving forward on improving the
safety of dietary supplements involves good manufacturing processes
(GMPs). More than five years ago, an assembly of industry groups
drafted a standard for GMPs, but the FDA has yet to publish a final
rule on this proposal.[258] Approximately 90 percent of manufacturers use
the warning label that was created for ephedra, but there are still
enough companies in existence that do not that can cause harm to
the public.[259] This requirement alone will not sufficiently
address the major issues with the regulation of dietary
supplements, but because the solution will involve several minor
and major changes, each effort will move the FDA and the industry
closer to that goal.

Reallocating Responsibility

One way in which the FDA has already attempted to
affect change without additional sources of funding from Congress
is through redistributing task responsibility between two different
centers under the FDA in order to increase efficiency and accuracy.
This action has come under fire by trade associations.[260] The Center for Drug Evaluation and Research
(CDER) will now be responsible for determining whether product
labels purport to cure diseases.[261] This decision has troubled CRN and other
trade associations because they fear that such a move brings
dietary supplements closer to being regulated as a drug.[262] The trade associations argue that DSHEA made it
clear that dietary supplements should be regulated as foods, and
therefore should be under the control of CFSAN.[263] But this argument does not take into
consideration the lack of funding.[264] The FDA needs additional funding to carry out
the plans to change their current system. If the FDA can get
another one of their centers to assist in the problem with clearly
defined instructions that would comply with DSHEA, it seems that
the associations' complaints are without merit. Ideally, the FDA
would be able to establish a center or committee dedicated only to
the dietary supplement industry.

Labeling

The change involving CDER follows in the wake of
the Pearson v. Shalala decision in which the court held that
particular health claims were protected by the First
Amendment.[265] The court of appeals disagreed with the FDA's
argument that certain health claims are "inherently misleading" and
can be disallowed on that basis.[266] In fact, the court remarked that "this
contention is almost frivolous."[267] Furthermore, the court held that the standard
of "significant scientific agreement" was far too vague and needed
to be clarified.[268] More disturbing was the risk assessment the
court performed. It did not consider the fact that risks are
relative and serious adverse events have been documented.[269] There is risk with many drugs, but at least
there is quantifiable benefit.[270] With dietary supplements, the risks and benefits
are not well understood.[271] Unlike the district court, the court of appeals
framed the issue primarily around First Amendment rights rather
than on the governmental interest of protecting the health and
safety of the public.[272] However, the court of appeals did not seem to
take into consideration that the Supreme Court has asserted that
the First Amendment does not prevent the government from "ensuring
that the stream of commercial information flows cleanly as well as
freely."[273] The court of appeals did not agree that
disclaimers and warnings are insufficient to solve the problem of
consumer deception.[274] This case demonstrates the complex issues and
difficulties dietary supplements pose in terms of regulation.

The industry is anxiously waiting to see how the
decision will be implemented.[275] Labeling is a thorn in the side both the FDA and
the industry. Many fear that the FDA will create two different
types of claims under the Nutrition Labeling and Education Act
(NLEA).[276] One type would be approved as truthful and not
misleading without the need for disclaimers, while the other would
be approved only with disclaimers.[277] Naturally the trade wants to ensure as much
control and freedom over labeling as possible. Another possible
result of this decision is that drug manufacturers may attempt to
spare the costly expense of clearing the hurdles drugs must meet,
and instead use herbal forms of the substance when possible in
order to get the product to market faster and with fewer
restrictions.[278] In the meantime, until comprehensive studies are
completed, requiring an additional statement that is prominently
placed in bold on the package that states "DO NOT MIX THIS
SUPPLEMENT WITH ANY PRESCRIPTION MEDICATION WITHOUT THE ADVICE OF
YOUR PHYSICIAN, AT THE RISK OF SERIOUS INJURY" would possibly be an
effective method to prevent unnecessary adverse events.[279] This statement on packaging brings the FDA
closer to achieving its goal of increased public awareness.

Education and Awareness

Educating the public by disseminating information
on ephedra should be one of the first tactics to try to combat this
extremely misunderstood herb. This will serve to correct the
problematic and faulty equation most people subscribe to so that
eventually the general public will come to realize that natural
does not equal safe. Such an approach should also notify consumers
to be savvy in their dietary supplement purchases. Consumers must
be instructed to be more aware that labels need to be read because
in many instances, they have no idea they are taking the
herb.[280]

Efforts have been made on the part of the FDA and
the FTC to inform the public, but the messages are not reaching a
broad enough audience. The FDA has a newsletter that uncovers many
"top health frauds," while the FTC also has publications to inform
the public on how to identify fraudulent claims.[281] The FTC has "advised" the public to be cautious
to avoid falling into the trap of thinking natural equals safe, but
what percentage of the public received this message? Clearly, the
message needs to be more effectively broadcast. Both the FDA and
the FTC have websites brimming with useful information that the
public has access to. The problem seems to be a lack of consumer
awareness about the sites and materials published. Many consumers
either lack the resourcefulness necessary to find the information,
or the time to seek it out. Therefore, the information is not
achieving the maximum potential impact it otherwise could have. The
message must be delivered to the public in such a way that it is
likely to be received.

An unusual possibility, television advertisements,
requires more funding, but it would be money well spent because it
would bring the FDA and FTC closer to their goals of protecting the
public through education and at a minimum, awareness. Placing
announcements on the big screen before the trailers begin in a
theater would be another opportunity to feature information in a
manner that will reach the intended audience. There is an
overwhelming amount of contradictory evidence available making it
impossible for most consumers to come to a conclusion in which they
feel certain. But, most consumers never bother to investigate due
to time constraints or a lack of knowledge as to where to begin
their search. Instead, most purchasers of dietary supplements get
their information from friends, labels, or sales people.[282] Perhaps using mainstream media is
unconventional, but the traditional approaches are not effective.
Thinking out of the box will push change further and faster than
contained thinking. It may require more effort and creative problem
solving skills than prior methods, but improvement in awareness is
well worth taking some risks.

Getting the information out is necessary to
counteract the role models such as Mark McGwire who has accredited
part of his achievement to ephedra products.[283] Even coaches and parents have encouraged their
athletes to ingest these wonder pills for a better performance and
physique.[284] For this target category, another appropriate
forum for dietary supplement education is the public schools.

In conjunction with the distribution of
information, the medical community needs to be better educated in
the field of herbal medicine. Even though many schools are adding
courses in alternative medicine to the classes they offer, and
doctors may attend them, they are not required to. A program
similar to the CLE course mandatory for lawyers would remedy this
gap created by the exploding consumer use of herbal medicines.

Formation of Alliances

It may be wise to form alliances with other
organization to deliver the messages to the public. Groups such as
Halt Ephedrine Abuse Today (H.E.A.T.) would be a natural choice
regarding this specific dietary supplement. This non-profit
organization was born after the death of the founding mother's 24
year-old son who died from ephedrine toxicity.[285] Their stated mission is: "to increase public
awareness about the dangers of ephedra and to promote the
prevention of abuse of ephedrine."[286] Other groups such as the American Heart
Association, the Herb Research Foundation, the Alliance for
Alternatives in Healthcare, the American Herbal Products
Association, and the Alternative Medical Association are but a few
additional examples of groups that should be contacted to join in
this informational alliance. They all have in interest in making
sure that the public does not misuse products that can lead to
serious side effects. Moreover, they also have an interest in
making sure that the public is made aware of any scientific
substantiation of natural products. This idea of alliance creation
has begun, but needs to continue. On May 14, 2001, the National
Center for Complementary and Alternative Medicine (NCCAM) at the
NIH arranged a "colloquium to explore opportunities to collaborate
with two key groups (industrial stakeholders who produce and label
dietary supplements, and organizations that develop and apply
standards to determine the quality and safety of these products)"
as well as many other groups (federal regulators, consumers,
practitioners of all types, researchers, publishers,
etc.).[287] This effort demonstrates the perceived value and
necessity of such alliances.

The alliances have the potential to be instrumental
in redesigning the adverse event monitoring system. For this
reason, before making changes to the system, the FDA should
assemble representation from the industry in order to create the
most effective system. Secondly, funding for the computer systems
and personnel to analyze the data must be considered.[288] These systems are crucial to the understanding
and documentation of the side effects of dietary supplements. If
the systems and processes are inadequate then the data collected
has little to no scientific value.

Mandatory Contribution from the Industry

A more controversial solution that is sure to be
met with fierce opposition from dietary supplement manufacturers is
a requirement that would make the industry responsible for funding
the necessary scientific studies that are at the epicenter of the
controversy over the safety and efficacy of these dietary
supplements. Each company could be required to donate a percentage
of their profits for the studies, provided they produce a product
with the targeted ingredient. DSHEA lifted their burden of proof
and opened the door to a thriving fraudulent sector of the
industry. Using the German Commission E, the Physician's Desk
Reference for Herbal Medicines, the National Center for
Complementary and Alternative Medicine, and the database begun by
the Office of Dietary Supplements at NIH is a decent beginning
point for these studies in the effort to create more accurate and
thorough monographs.[289] These monographs can lend credibility to the use
of dietary supplements, which have the added effect of making
patients more comfortable with informing their physicians of their
use of dietary supplements.

This financial burden would not restrict the
current sales, marketing or production in place, but would ensure
more accurate information is ascertained as to the appropriate
dosages, dangerous interactions, and benefits of the supplement. If
in fact a supplement is found to be dangerous or toxic to the user
in its present form, then the FDA could act on this information. If
the supplements are as safe and effective as they claim to be, the
industry should have no contention over such a plan--except for the
gouge it will make in their profitability and a concern for the
methodology of the testing. Alternatively, if the FDA could not
gain the support necessary to require this measure, they should
request additional funds to be able to lessen the financial burden
on companies.

Rating System

A rating system could be implemented to tackle the
problem of scientific agreement or substantiation.[290] The scale could rate herbs on a 1-5 basis for
effectiveness.[291] For example, if only anecdotal exists, the
product would receive a rating of 1, whereas a 5 could inform the
consumer that there is "significant scientific agreement" and the
product is indeed effective.[292] The ratings would need to be changed as new
information came available.[293] The companies could present any independent
research in order to change the monograph and hence the rating, but
it would have to be confirmed first.[294] Even with a rating system, until conclusive
studies and scientific agreement is reached, labeling in addition
to the ratings would be beneficial.

Heightened Surveillance

Random testing of products for contamination and
monitoring of label claims is yet another option for increasing the
safety of the consumers of dietary supplements, and it is within
the FDA's scope of authority.[295] The FDA has acknowledged that their current
surveillance efforts "could be improved."[296] This would hopefully deter the knowingly
fraudulent manufactures from using impurities in their products.
The downside of this suggestion is that it will require additional
funding in order to be carried out effectively.

Conclusion

The adverse events experienced after ingesting
ephedra and other dietary supplements have demonstrated the need
for FDA intervention. The FDA has an important role to play in
safeguarding the health and safety of the American public. The FDA
has been criticized as contravening the Congressional intent
underlying DSHEA because of its attempts to regulate the dietary
supplement industry, when in fact, the FDA has not overstepped its
bounds. The agency has only taken the measures it felt necessary to
protect the public and "implement a complex and ambiguous
law."[297] However, the FDA does need to focus on more
effective procedures and systems for collecting adverse event
reports and could take additional steps toward public awareness. In
order for the FDA to address the overall problems with the
regulating the dietary supplement industry efficiently and
effectively, they will need additional funding.